ABSTRACT: The epididymal dependence on androgens differs depending upon the region of the epididymis as well as the source of androgens- circulating androgens (CA) in the blood versus luminal androgens (LA) in the rete fluid. It is hypothesized that LA, CA, estrogens, or other components of the rete fluid differentially regulate the structure and function of different sub-regions of the caput epididymis (CE) and efferent ductules (ED). To test the hypothesis, we propose to study androgen receptors, estrogen receptors, profiles of secretory proteins, and histology in three sub-regions each of the CE and ED. Three experiments will be conducted: (1) Orchiectomy with and without testosterone implants; (2) extratesticular rete ligation with and without testosterone implants; and (3) orchiectomy with testosterone and estradiol implants and estradiol implant only. Both androgen and estrogen receptors will be examined with quantitative and immunocytochemical/autoradiographic methods. Profiles of secretory proteins will be analyzed by gel electrophoresis of the medium in which tissues will be incubated in vitro with (35S) methionine. The histology will include ultrastructural examination of organelles associated with absorption and protein synthesis. Whereas results of the first two experiments will reveal the role of androgens, especially the differential role between CA and LA, those of the third experiment will reveal the significance of estrogens. Overall, results will provide insights on the regulation of different regions of the CE and ED whose secretions play an important role in initiation of sperm maturation.